Branched-chain α-ketoacid dehydrogenase deficiency (maple syrup urine disease): Treatment, biomarkers, and outcomes

Publication date: Available online 16 January 2020Source: Molecular Genetics and MetabolismAuthor(s): Kevin A. Strauss, Vincent J. Carson, Kyle Soltys, Millie E. Young, Lauren E. Bowser, Erik G. Puffenberger, Karlla W. Brigatti, Katie B. Williams, Donna L. Robinson, Christine Hendrickson, Keturah Beiler, Cora M. Taylor, Barbara Haas-Givler, Stephanie Chopko, Jennifer Hailey, Emilie R. Muelly, Diana A. Shellmer, Zachary Radcliff, Ashlin Rodrigues, KaLynn LoevenAbstractOver the past three decades, we studied 184 individuals with 174 different molecular variants of branched-chain α-ketoacid dehydrogenase activity, and here delineate essential clinical and biochemical aspects of the maple syrup urine disease (MSUD) phenotype. We collected data about treatment, survival, hospitalization, metabolic control, and liver transplantation from patients with classic (i.e., severe; n = 176), intermediate (n = 6) and intermittent (n = 2) forms of MSUD. A total of 13,589 amino acid profiles were used to analyze leucine tolerance, amino acid homeostasis, estimated cerebral amino acid uptake, quantitative responses to anabolic therapy, and metabolic control after liver transplantation. Standard instruments were used to measure neuropsychiatric outcomes. Despite advances in clinical care, classic MSUD remains a morbid and potentially fatal disorder. Stringent dietary therapy maintains metabolic variables within acceptable limits but is challenging to implement, fails to restore app...
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research